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微流控技术在细菌趋化中的应用。

Microfluidics for bacterial chemotaxis.

机构信息

Ralph M Parsons Laboratory, Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Building 48, Room 335, 77 Massachusetts Ave, Cambridge, MA 02139, USA.

出版信息

Integr Biol (Camb). 2010 Nov;2(11-12):604-29. doi: 10.1039/c0ib00049c. Epub 2010 Oct 21.

Abstract

Microfluidics is revolutionizing the way we study the motile behavior of cells, by enabling observations at high spatial and temporal resolution in carefully controlled microenvironments. An important class of such behavior is bacterial chemotaxis, which plays a fundamental role in a broad range of processes, including disease pathogenesis, biofilm formation, bioremediation, and even carbon cycling in the ocean. In biophysical research, bacterial chemotaxis represents a powerful model system to understand how cells and organisms sense and respond to gradients. Using microfluidics to study chemotaxis of free-swimming bacteria presents experimental challenges that are distinct from those arising in chemotaxis studies of surface-adherent cells. Recently, these challenges have been met by the development of advanced microdevices, able to generate flow-free, steady gradients of arbitrary shape. Much attention to date has been focused on tool development. Yet, we are now at an exciting turning point where science begins to balance technology. Indeed, recent microfluidic studies provided new insights on both the mechanisms governing bacterial gradient sensing (e.g. tuning of response sensitivity, discrimination between conflicting gradients) and the large-scale consequences of chemotaxis (e.g. in the oceans). Here we outline the principles underlying recently proposed gradient generators for bacterial chemotaxis, illustrate the advantage of the microfluidic approach through selected examples, and identify a broader set of scientific questions that may now be addressed with this rapidly developing technology. The latest generation of microfluidic gradient generators, in particular, holds appeal for both biophysicists seeking to unravel the fundamental mechanisms of bacterial chemotaxis, and ecologists wishing to model chemotaxis in realistic environments. Time is ripe for a deeper integration between technology and biology in fully bringing to bear microfluidics on studies of this fascinating microbial behavior.

摘要

微流控技术正在彻底改变我们研究细胞运动行为的方式,使我们能够在精心控制的微环境中以高时空分辨率进行观察。这种行为的一个重要类别是细菌趋化性,它在广泛的过程中起着基本作用,包括疾病发病机制、生物膜形成、生物修复,甚至海洋中的碳循环。在生物物理研究中,细菌趋化性代表了理解细胞和生物如何感知和响应梯度的强大模型系统。使用微流控技术研究自由游动细菌的趋化性会带来与表面附着细胞趋化性研究中不同的实验挑战。最近,通过开发能够产生任意形状的无流动、稳定梯度的先进微器件,这些挑战已经得到了满足。迄今为止,人们的注意力主要集中在工具的开发上。然而,我们现在正处于一个令人兴奋的转折点,科学开始与技术相平衡。事实上,最近的微流控研究为细菌梯度感应的机制(例如响应灵敏度的调节、冲突梯度之间的区分)和趋化性的大规模后果(例如在海洋中)提供了新的见解。在这里,我们概述了最近提出的细菌趋化性梯度发生器的原理,通过选择的例子说明了微流控方法的优势,并确定了一组更广泛的科学问题,这些问题现在可以通过这项快速发展的技术来解决。特别是最新一代的微流控梯度发生器,对寻求揭示细菌趋化性基本机制的生物物理学家和希望在现实环境中模拟趋化性的生态学家都具有吸引力。现在是将技术和生物学更深层次地结合起来,充分利用微流控技术研究这种迷人的微生物行为的时候了。

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